Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America.
PLoS One. 2010 Feb 1;5(2):e8898. doi: 10.1371/journal.pone.0008898.
Although microRNAs are being extensively studied for their involvement in cancer and development, little is known about their roles in Alzheimer's disease (AD). In this study, we used microarrays for the first joint profiling and analysis of miRNAs and mRNAs expression in brain cortex from AD and age-matched control subjects. These data provided the unique opportunity to study the relationship between miRNA and mRNA expression in normal and AD brains. Using a non-parametric analysis, we showed that the levels of many miRNAs can be either positively or negatively correlated with those of their target mRNAs. Comparative analysis with independent cancer datasets showed that such miRNA-mRNA expression correlations are not static, but rather context-dependent. Subsequently, we identified a large set of miRNA-mRNA associations that are changed in AD versus control, highlighting AD-specific changes in the miRNA regulatory system. Our results demonstrate a robust relationship between the levels of miRNAs and those of their targets in the brain. This has implications in the study of the molecular pathology of AD, as well as miRNA biology in general.
尽管 microRNAs 因其在癌症和发育中的作用而被广泛研究，但它们在阿尔茨海默病 (AD) 中的作用知之甚少。在这项研究中，我们首次使用微阵列联合分析了 AD 和年龄匹配对照受试者大脑皮层中的 miRNA 和 mRNA 表达。这些数据为研究正常和 AD 大脑中 miRNA 和 mRNA 表达之间的关系提供了独特的机会。使用非参数分析，我们表明许多 miRNA 的水平可以与它们的靶 mRNA 呈正相关或负相关。与独立的癌症数据集进行比较分析表明，这种 miRNA-mRNA 表达相关性不是静态的，而是依赖于上下文的。随后，我们确定了一组大量的 miRNA-mRNA 关联，这些关联在 AD 与对照之间发生了变化，突出了 miRNA 调节系统在 AD 中的特异性变化。我们的结果表明，miRNA 和它们在大脑中的靶标之间存在着强大的关系。这对 AD 的分子病理学研究以及一般的 miRNA 生物学都具有重要意义。
